UNASSIGNED: Pernicious anemia (PA) is believed to be highly prevalent in Western countries but has rarely been reported in China. The study explores whether PA, an autoimmune disease, is an uncommon cause of cobalamin (vitamin B12) deficiency anemia in China.
UNASSIGNED: Clinical and hematological data were collected from 90 cobalamin deficiency-caused megaloblastic anemia (MA) patients between July 2014 and December 2021. Through anti-intrinsic factor antibody (IFA) and anti-parietal cell antibody (PCA) testing, PA was distinguished from other causes of cobalamin deficiency leading to MA. Meanwhile, 30 healthy controls (HCs) were included to estimate the positive rates of IFA and PCA.
UNASSIGNED: Of the 30 HCs, only one tested positive for IFA, and all 30 tested negative for PCA. Among the 90 patients with cobalamin deficiency-caused MA, 76.7% were positive for IFA, and 47.8% were positive for PCA; a total of 76 patients (84.4%) were diagnosed with PA. The mean follow-up time was 41.0 ± 16.3 months. During the follow-up period, no case relapsed among the continuous cobalamin-supply treatment patients, while 24.4% of patients relapsed due to the interruption of maintenance cobalamin-supplement therapy (the median recurrence time was 54.0 ± 17.7 months).
UNASSIGNED: The proportion of PA in cobalamin deficiency-caused MA patients in Hainan province was higher than 80%, which was more common than expected. Therefore, screening for IFA, PCA, endoscopic biopsy, and thyroid-related parameters are recommended for all cobalamin deficiency-caused MA patients. Furthermore, maintenance cobalamin-supplement therapy is important for PA patients.
This research examines pernicious anemia (PA), a type of anemia caused by vitamin B12 deficiency, which has been widely reported in Western countries but is less known in China. The study focuses on determining if PA is also a significant cause of this deficiency in Hainan, China. Researchers gathered data from patients with megaloblastic anemia (a blood disorder) due to lack of vitamin B12, comparing them with healthy individuals to see how common PA is. The findings reveal that a very high percentage of the patients studied have PA, much higher than expected. This suggests that PA is not as rare in this region of China as previously thought. The study also highlights the importance of continuous treatment with vitamin B12 to prevent the recurrence of the anemia. Based on these results, the researchers recommend that all patients with vitamin B12 deficiency should be tested for PA and continuously receive vitamin B12 supplements to maintain their health once diagnosed with PA. This strategic insight is of paramount importance to medical practitioners in China, potentially paving the way for enhanced clinical management protocols for individuals afflicted by this ailment.

Visual analysis of the current status, research hotspots, evolving trends, and future prospects in the field of thiamine-responsive megaloblastic anemia syndrome (TRMA), providing new insights and directions for subsequent research on the pathogenic mechanisms and prevention strategies of TRMA. Taking the core database of Web of Science as the literature source, selecting TRMA-related literature records published from 1997 to 2023 as the research object, and using R software and Citexs database to conduct visual analysis and discussion of the research content. The results showed that a total of 89 publications related to the topic were published from 1997 to 2023, with an average annual publication volume of 3 papers. Classified by country, it was found that the United States, and Israel among other countries and institutions, published a significant number of papers. Through keyword frequency analysis, high frequencies of keywords such as diabetes, deafness, thiamine-responsive megaloblastic anemia, and mutations in the solute carrier family 19 member 2 (SLC19A2) gene were observed, indicating that to date, these keywords have been the main research directions, highlighting a gradually reached consensus on the mechanism exploration of TRMA. In conclusion, TRMA research focuses on the mechanisms of hot topics such as diabetes, deafness, and thiamine-responsive megaloblastic anemia, and the core gene SLC19A2 research may currently become a new breakthrough point for future molecular studies.
对硫胺素响应性巨幼细胞贫血综合征（thiamine-responsive megaloblastic anemia syndrome，TRMA）研究领域的现状、研究热点、演变趋势和未来展望进行可视化分析，为TRMA发病机制的后续研究与防治策略提供新的思路和方向。本研究以Web of Science核心数据库为文献来源，以1997—2023年间发表的TRMA相关文献记录为研究对象，利用R软件及Citexs数据库对研究内容进行可视化分析和讨论。结果显示，1997—2023年共发表相关文献89篇，文献年均发文量3篇。按国家分类，发现美国和以色列等国家和机构发表论文较多。通过关键词频率分析，糖尿病、耳聋、硫胺素响应性巨幼细胞贫血及溶质载体家族19成员2（SLC19A2）基因突变等关键词出现的频率高，表明至今以上述关键词作为主要研究方向，凸显了对TRMA的机制探索逐渐达成共识。综上，当前TRMA以糖尿病、耳聋、硫胺素响应性巨幼细胞贫血等为研究热点，而核心基因SLC19A2的研究可能成为未来分子研究的新突破点。.

BACKGROUND: Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is considered as a safe and effective treatment option, with generally good tolerance. Diarrhea and rash are the most common side effects, and more rare side effects appear in long-term real-world applications. Severe erlotinib related megaloblastic anemia is rare and remains unreported. This is the first case report of severe megaloblastic anemia in a patient with advanced lung adenocarcinoma with an EGFR L858R mutation treated with erlotinib. In this report, the clinical manifestations, diagnosis and treatment of erlotinib related severe megaloblastic anemia are described, and the possible pathogenesis and related treatment options are discussed.
METHODS: Herein, we present a 57- year-old non-smoking female diagnosed with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, who had received erlotinib as the first-line therapy. After 44 weeks of treatment, the patient developed severe anemia. Anemia was manifested as megaloblastic anemia with elevated mean corpuscular volume and mean corpuscular hemoglobin. The total vitamin B12 level was below the detection limit of 50.00 pg /mL. Bone marrow smear suggested megaloblastic anemia. Her hematologic parameters were markedly recovered following the withdrawal of erlotinib and vitamin B12 supplement. As a result, the patient was diagnosed with erlotinib-associated megaloblastic anemia.
CONCLUSIONS: This is the first case of severe megaloblastic anemia reported with erlotinib. Few of these hematologic adverse effects have been observed in studies on erlotinib, this case report highlights this possibility for long-term erlotinib administration. Close clinical and blood monitoring is recommended for patients receiving long-term TKI therapy.

暂无摘要。

This study aims to evaluate the differences in CD105+ nucleated erythroid cell (NEC) immunophenotypes between myelodysplastic syndrome (MDS) and megaloblastic anemia (MA) using multiparameter flow cytometry and to screen potential markers. We analyzed bone marrow sample data from 37 patients with MDS, 35 with MA, 53 with iron-deficiency anemia (anemic controls), and 35 without anemia (normal controls). Compared with normal controls, the MDS and MA groups showed a decrease in the proportion of CD117+CD105+NEC and the relative mean fluorescence intensity (RMFI) of CD71 in CD105+NEC, accompanied by an increase in the coefficient of variation (CV) of CD71 and CD36. Additionally, CD36 RMFI of CD105+NEC increased in the MA group. Compared with anemia controls, the MDS and MA groups showed a significant increase in CD36 CV of CD105+NEC, and the CD36 RMFI in the MA group increased while that in the MDS group decreased. The proportions of CD117+CD105+NEC, CD36 CV, and CD36 RMFI in CD105+NEC differed significantly between MDS and MA groups. Among them, CD36 RMFI had good diagnostic performance (area under the curve: 0.844, 95% confidence interval: 0.753-0.935). CD36 RMFI of CD105+NEC may be a helpful marker in differentiating MDS and MA using multiparameter flow cytometry.

Objective: To investigate the lifespan of erythrocytes in megaloblastic anemia (MA) patients. Methods: A prospective cohort study analysis. Clinical data from 42 MA patients who were newly diagnosed at the Department of Hematology, Lanzhou University Second Hospital from January 2021 to August 2021 were analyzed, as were control data from 24 healthy volunteers acquired during the same period. The carbon monoxide breath test was used to measure erythrocyte lifespan, and correlations between erythrocyte lifespan and laboratory test indexes before and after treatment were calculated. Statistical analysis included the t-test and Pearson correlation. Results: The mean erythrocyte lifespan in the 42 newly diagnosed MA patients was (49.05±41.60) d, which was significantly shorter than that in the healthy control group [(104.13±42.62) d; t=5.13,P=0.001]. In a vitamin B12-deficient subset of MA patients the mean erythrocyte lifespan was (30.09±15.14) d, and in a folic acid-deficient subgroup it was (72.00±51.44) d, and the difference between these two MA subsets was significant (t=3.73, P=0.001). The mean erythrocyte lifespan after MA treatment was (101.28±33.02) d, which differed significantly from that before MA treatment (t=4.72, P=0.001). In MA patients erythrocyte lifespan was positively correlated with hemoglobin concentration (r=0.373), and negatively correlated with total bilirubin level (r=-0.425), indirect bilirubin level (r=-0.431), and lactate dehydrogenase level (r=-0.504) (all P<0.05). Conclusions: Erythrocyte lifespan was shortened in MA patients, and there was a significant difference between a vitamin B12-deficient group and a folic acid-deficient group. After treatment the erythrocyte lifespan can return to normal. Erythrocyte lifespan is expected to become an informative index for the diagnosis and treatment of MA.
目的： 研究巨幼细胞性贫血（MA）患者的红细胞寿命变化。 方法： 前瞻性队列研究。收集2021年1至8月于兰州大学第二医院血液科初诊为MA的42例患者，以同期24名健康志愿者为对照。采用测定内源性一氧化碳呼气试验法检测红细胞寿命，观察MA患者红细胞寿命变化及其与实验室检查指标的相关性。统计学分析主要采用t检验及Pearson相关性分析。 结果： 42例初诊MA患者的红细胞寿命为（49.05±41.60）d，较健康对照的（104.13±42.62）d明显缩短（t=5.13，P=0.001）。MA患者中，维生素B12缺乏患者的红细胞寿命为（30.09±15.14）d，叶酸缺乏患者的红细胞寿命为（72.00±51.44）d，二者差异有统计学意义（t=3.73，P=0.001）。MA治疗后红细胞寿命为（101.28±33.02）d，高于治疗前（t=4.72，P=0.001）。相关性分析显示，MA患者红细胞寿命与血红蛋白浓度呈正相关（r=0.373），与总胆红素水平（r=-0.425）、间接胆红素水平（r=-0.431）、乳酸脱氢酶水平（r=-0.504）呈负相关（均P<0.05）。 结论： MA患者红细胞寿命缩短，叶酸缺乏与维生素B12缺乏患者红细胞寿命有差别，治疗后红细胞寿命可恢复正常，红细胞寿命有望成为MA诊治的重要指标。.

Subacute combined degeneration of the spinal cord (SCD) is mainly caused by deficiency of Vitamin B12 and characterized by deep hypoesthesia, sensory ataxia and spasmodic paralysis of lower limbs. SCD often accompanies with megaloblastic anemia. Psychiatric symptoms could be the initial manifestations of SCD by lack of Vitamin B12, but are rarely considered secondary to physical discomfort and psychological factors in SCD. Additionally, treatment experience for psychiatric symptoms in SCD remains little reported.
We presented a case of a 37-year-old female who complained of being persecuted and controlled for one week and thus was admitted to the psychiatry department. Before that, she had went through persistent paresthesia and numbness of her lower extremities for two-month. Low Vitamin B12 level and hemoglobin concentration, neurologic symptoms and bone marrow smear results supported the clinical diagnosis of SCD and megaloblastic anemia. With supplementation of Vitamin B12 and blood transfusion and short-term prescription of antipsychotics and antidepressants, physical symptoms were improved and psychological symptoms disappeared within 2 weeks.
Psychiatric symptoms of SCD could be generated from lack of Vitamin B12, anemia and neurologic symptoms, where short-term use of antipsychotics and antidepressants may be effective.

暂无摘要。

The clinical data of two children with Imerslund-Gräsbeck syndrome (IGS) who were admitted to the First Affiliated Hospital of Zhengzhou University in August 2019 was analyzed retrospectively. The two cases were siblings, aged 8 years and 8 months and 6 years and 2 months, respectively. These two boys had megaloblastic anemia, low level of vitamin B12, hyperhomocysteinemia, accompanied by proteinuria and renal tubular injury, while they showed normal folate level and renal function. Blood tandem mass spectrometry and urine organic acid analysis suggested methylmalonic acidemia (MMA). The initial diagnosis was MMA with homocysteinemia. No known pathogenic gene mutation related to MMA was found by gene sequencing. Compound heterozygous variants of amnionless (AMN) gene were detected: c.43+5G>A and c.C717G. The corrected diagnosis was IGS. Both brothers were treated with long-term intramuscular injection of vitamin B12. After follow-up for one year, these two cases had no clinical symptoms, and their blood indicators remained normal, but proteinuria and renal tubular injury persisted. Blood tandem mass spectrometry and urine organic acid analysis alone may easily lead to misdiagnosis, but combined with genetic testing can improve the accuracy of diagnosis of IGS. Lifelong parenteral vitamin B12 replacement therapy can effectively reverse the clinical and biochemical results, but is uncertain in alleviating albuminuria and renal tubule injury. It\'s necessary to monitor the renal function regularly.
回顾分析郑州大学第一附属医院2019年8月收治的两例Imerslund-Gräsbeck综合征（IGS）患儿的临床资料。两例患儿为同胞兄弟，年龄分别为8岁8个月和6岁2个月，检查均示巨幼红细胞性贫血，血清维生素B12减低，血同型半胱氨酸明显升高，叶酸测定及肾功能均正常，均伴有蛋白尿、肾小管损伤。血串联质谱及尿有机酸分析示甲基丙二酸血症（MMA）。初诊为MMA伴同型半胱氨酸血症。基因测序未发现与MMA相关的已知致病基因突变，检测到AMN基因的复合杂合变异：c.43+5G>A和c.C717G。修正诊断为IGS，给予长期肌内注射维生素B12治疗，随访1年，无临床症状，血指标正常，但蛋白尿及肾小管损伤持续。单靠血串联质谱及尿有机酸分析易造成误诊，联合基因检测可提高IGS的诊断。终生肠外维生素B12替代治疗可有效逆转临床和生化结果，但对蛋白尿及肾小管损伤疗效待定，定期监测肾功能是必要的。.

OBJECTIVE: Thiamine-responsive megaloblastic anemia (TRMA), caused by SLC19A2 loss-of-function variants, is characterized by the triad of megaloblastic anemia, progressive sensorineural deafness, and non-type 1 diabetes mellitus. Here, we present the case of a Chinese infant with two novel variants segregating in compound heterozygous form in SLC19A2 and reviewed genotype-phenotype associations (GPAs) in patients with TRMA.
METHODS: Whole-exome sequencing was performed to establish a genetic diagnosis. The clinical manifestations and genetic variants were collected by performing a literature review. The bioinformatics software SIFT, PolyPhen2, and Mutation Taster was applied to predict variant effects and analyze GPAs.
RESULTS: Two novel variants segregating in compound heterozygous form in SLC19A2 (NM_006996.2: exon2:c.336_363del:p.W112fs; exon2:c.358G>T:p.G120X) was identified. Thiamine supplementation corrected anemia and diabetes mellitus but did not improve the hearing defect. In the literature, 183 patients with TRMA with 74 variants in SLC19A2 have been reported, with high incidence in the Middle East, South Asia, and the northern Mediterranean. Patients with biallelic premature termination codon variants presented with more severe phenotypes, and truncating sites on extracellular domains was a protective factor for the hemoglobin level at diagnosis.
CONCLUSIONS: Two novel compound heterozygous variants (NM_006996.2: exon2:c.336_363del:p.W112fs; exon2:c.358G>T:p.G120X) were identified, and GPAs in TRMA indicated the predictability of clinical manifestations.